The objective of this proposal is to continue the activities of an established Program Project involving seven senior scientists who are currently studying the effects of aging on the central nervous system. The studies in this Program Project encompass interdisciplinary analyses designed to describe the process of senescence in a variety of neuronal systems in aged cats and rats. We believe that the paucity of fundamental descriptive data of senescent neural functioning and the interdependence of neural processes argue forcibly for investigations encompassing more than one discipline or a single system. Through idiosyncratic and collaborative studies, we will carry out multidisciplinary experiments dealing with sensory, motor and integrative systems in which we have already found age-related decrements in structure and/or function. These investigations will, in most cases, be performed on the same individual experimental animal, thus vastly improving our resolution of age-determined processes of neural deterioration. We expect to obtain data that will illuminate not only senescent changes, but which will also describe those sites and systems that are relatively or completely resistant to the aging process. The age-related deficits of different elements in our focused areas of investigation should provide a microcosm of interrelated time-dependent changes throughout the nervous system. By this means we expect to generate data that will provide a basis for understanding one of the most debilitating pathologies of old age--Alzheimer's disease; in our experimental anaimals we have already found aged changes which are similar to those reported in humans suffering from this disease. A major portion of our research efforts are currently devoted to this Program Project and we expect to maintain a dedicated commitment to research on aging in the central nervous system in the years to come.